The invention relates to bioimplantable articles having a bioactive ceramic coating, which reassembles bone mineral, and to methods for forming such coating on implantable articles.
It is desirable to apply mineralized and/or ceramic coatings to a variety of articles. Biological implants including joint prostheses and dental implants represent one class of articles to which such coatings are frequently applied. The substrate to which these coatings is applied is usually a metal or a plastic, but the coatings can be applied to other substrates such as ceramic and silicon.
Biological implants, such as joint and dental prostheses, usually must be permanently affixed or anchored within bone. In some instances it is acceptable to use a bone cement to affix the prosthesis within bone. In the case of many joint prostheses, however, it is now more common to affix the joint prosthesis by encouraging natural bone ingrowth in and around the prosthesis. Bone-to-implant interfaces that result from natural bone ingrowth tend to be stronger over time and more permanent than are bone cement-prosthesis bonds.
Optimal bone ingrowth requires that natural bone grow into and around the prosthesis to be implanted. Bone ingrowth and prosthesis fixation can be enhanced by providing irregular beaded or porous surfaces on the implant. Although various materials, including titanium alloys, are biocompatible, they are not necessarily bioactive because they can neither conduct bone formation nor form chemical bonds with bone.
Thus, enhanced fixation of implants within bone can be attained by coating the implant with a bioactive mineralized and/or ceramic material. Such coatings have be shown to encourage more rapid bone ingrowth in and around the prosthesis.
Various techniques are used to apply mineralized and/or ceramic coatings to bioimplantable substrates. These coatings are typically made of ceramics and tend to be characterized by a relatively large crystal size. These coatings can be applied by a variety of techniques including plasma spraying, ion implantation, and sol-gel processing. These coating methods, although relatively widely used, do have some drawbacks. For example, the applied coatings tend to possess micropores and macropores and they can be relatively thick and brittle. These coatings can also possess chemical defects, and they do not always adhere well to substrates. Finally, such coatings are not evenly and uniformly applied to surfaces with complex geometries, such as porous surfaces with undercut regions.
It has been well documented that calcium phosphate ceramics, especially hydroxyapatite, can conduct bone formation. Hydroxyapatite ceramic has been successfully applied as a coating on cementless metallic implants to achieve quick and strong fixation. Thermal plasma spraying is one of the more common methods used to produce hydroxyapatite coatings. However, the resulting plasma-sprayed hydroxyapatite coating is of relatively low density and is not uniform in structure or composition. The adhesion between the coating and substrate is generally not very strong, especially after long term exposure within the body. The generation of hard ceramic particles, resulting from the degradation of thermal plasma sprayed coating, and coating delamination, are major concerns.
Low temperature processes have also been implemented to produce hydroxyapatite ceramic coatings using water-based solutions. Since aqueous solutions can reach any open space, these low-temperature processes can be efficiently used in the case of substrates with complex surface geometries. The hydroxyapatite coating that is formed from this solution can be more biologically friendly to bone tissue than is the plasma-sprayed hydroxyapatite coating which is produced by a high temperature process. However, currently known low temperature processes typically require pretreatment of the substrate.
The calcium phosphate ceramic made of hydroxyapatite [HA, Ca10(PO4)6(OH)2] has been demonstrated to be capable of inducing bone formation and bonding to bone. Because of this osteoconductive property, HA ceramic has been used in repair of bone defects. Metallic implants are often coated with HA ceramic to allow a rapid bond apposition and thereby to entail fixation of the implants in bone without use of bone cement.
One example of an aqueous system-based coating technique is disclosed in U.S. Pat. No. 5,205,921 in which bioactive ceramic coatings are electrodeposited upon a substrate. Bunker et al., Science 264, 48-55 (1994) disclose a technique for applying an octacalcium phosphate upon a substrate by immersing the substrate in a solution containing calcium chloride after surface treating the substrate with a material such as chlorosilane. Other techniques, such as disclosed in Japanese Patent Application No. 8-40711, form a hydroxyapatite coating by exposing the substrate to calcium phosphate in a pressure reactor. U.S. Pat. No. 5,188,670 discloses a technique for forming a hydroxyapatite coating on a substrate by directing a stream of liquid containing hydroxyapatite particles to apply a fibrous, crystalline coating of hydroxyapatite.
Bone mineral is a calcium phosphate with apatite structure. Bone apatite contains hydrogenophosphate (HPO42xe2x88x92) ions, carbonate (CO32xe2x88x92) ions, magnesium (Mg2+) ions, sodium (Na+) ions and other trace ions, with sodium and magnesium ions substituting for a percentage of calcium ions in the apatite structure and with carbonate ions substituting for PO43xe2x88x92 and OHxe2x88x92 in hydroxyapatite.
Chemically absorbed water is found in bone apatite. In addition to these chemical features, bone apatite is generally found in the form of nanocrystals which are poorly crystallized as seen in X-ray diffraction patterns. Bone apatite typically is formed from a physiological solution, namely blood plasma at body temperature in a process called bone mineralization. The organic matrix synthesized by bone cells plays a crucial role in initiating bone apatite formation.
Although HA and bone apatite belong to the same apatite family, they are different. HA ceramic in use today is different from bone apatite in terms of composition, structure and the way they are formed. For example HA contains hydroxyl groups whereas bone apatite does not include hydroxyl functionality or is essentially devoid of hydroxyl functionality, e.g., the hydroxyl content is below current methods of analytical detection. In contrast to hydroxyapatite, bone apatites generally include water molecules within the crystal structure. Furthermore, plasma-sprayed HA coatings are very different from bone mineral apatite, possessing various calcium phosphate salts.
Despite the existence of ceramic coatings and various processes for producing such coatings, there remains a need for improved and reliable processes used to apply bioactive ceramic coatings to substrates.
The invention provides a dense, substantially pure ceramic coating with a crystal size of less than 1 micrometer. The coating forms a good chemical bond to substrates to which it is applied. Preferably, the coating is a bioactive ceramic coating in the form of a bone mineral carbonated nano-crystalline apatite with chemically adsorbed water having a crystal size of less than about 1 micrometer. The coating contains calcium, magnesium, carbonate and phosphate. Optionally, the coating also includes ions or ionic groups selected from the group consisting of sodium, chlorine, sulfates, silicate and mixtures thereof. Preferably, the ratio of carbonate groups to phosphate groups in the coating is in the range of about 1:100 to 1:3. Further, the atomic ratio of magnesium to calcium is in the range of about 1:100 to 1:4.
One aspect of the present invention is to provide a medical implant with a thin film of a synthetic apatite that is equivalent to, or substantially equivalent to naturally occurring bone apatite composition and its structure. The synthetic apatite film is formed by an soaking implant in an aqueous solution containing calcium, phosphate and bicarbonate ions which allows the apatite to grow on the surfaces of the implants in a crystalline state, i.e., not amorphous. Interaction of bicarbonate ions with the atmosphere above the solution raises the pH of the solution to a pH range of from about 6.5 to about 7.5 as is required for the growth of the synthetic bone apatite film. The synthetic bone apatite film produced by this process, results in an effective bone composition that promotes bone ingrowth and thereby provides implants with bone-bonding properties. The synthetic apatite film can also be used to attract biological molecules such as growth factors for further improvement of bone growth.
The coating can be applied to a variety of substrates, including silicon, metals, ceramics, and polymers. It is particularly useful for application to bioimplantable substrates such as bone and dental prostheses. The coating can be uniformly applied to substrate surfaces that have complex geometries and surface features, including porous beaded substrates. The thickness range of the coating can vary from about 0.005 to 50 micrometers.
The coating can be effectively and efficiently applied to a variety of substrates. According to the method of the invention, there is first provided an aqueous solution comprising calcium, magnesium, phosphate, and carbonate ions with a pH in the range of about 5-10 and temperature less than about 100xc2x0 C. Optionally, the solution also includes ions of sodium, potassium, chlorine, sulfate, silicate and mixtures thereof. A suitable substrate is then at least partially immersed in the solution for an amount of time sufficient for the solution to react with the substrate to form a bone mineral ceramic coating and effect the chemical bonding of the coating to the substrate. During the process the solution can be exposed in a controlled environment to an artificial atmosphere having about 0.0001 to 10 mole percent carbon dioxide and a balance of gas or gases selected from the group consisting of oxygen, nitrogen, argon, hydrogen, water steam, ammonia, and mixtures thereof. One particular advantage of the process of the invention is that the coating can be applied at ambient pressures.